In collaboration with our colleagues at the other five WIHS sites and WDMAC, we are proposing to be active contributors to the research agenda described in Part A of this application which, with the expanded cohort, can substantively contribute to an understanding of HIV infection in women in the era of effective antiretroviral therapy. Although SUNY looks forward to providing completed data sets, meticulously collected and stored biologic specimens, and its investigators' expertise to the full range of issues that WIHS will confront, we believe we have particular strengths. Specifically, we have successfully served as a source for a disproportionate share of study data, biologic samples and participants in substudies and have demonstrated our ability to seamlessly incorporate additional study participants into the expanded study population. We have been uniquely successful at working to overcome barriers to recruitment and retention in both the core study and within substudies. Our investigators have a particular academic focus on obstetric and gynecologic, behavioral, epidemiologic and co- infection aspects of HIV infections in women, have demonstrated the ability to collaborate with researchers from other locations and disciplines and have committed themselves intellectually to new areas of scientific investigation in the WIHS. Finally, the scientific environment at SUNY, which has supported research into HIV infection in women for over fifteen years, augurs well for the success of the site. In order to demonstrate this site's ability to perform significant scientific analyses of WlHS data, in this application we propose to define the relationship between smoking, inflammatory markers, genetic polymorphisms and the prognosis of women with HIV. The majority of WlHS participants smoke and researchers at SUNY have found that smoking influences changes in CD4 cell count and HIV-1 RNA with smokers having a significantly higher mortality and less response to HAART. It is not known whether these effects vary with genetic polymorphisms. Smoking may also influence inflammatory markers of disease progression (e.g., albumin) and the course of cervical disease. We will perform a pilot study of 500 women smokers in which data will be obtained on genetic polymorphisms and selected markers of inflammation (albumin, prealbumin and CRP). The design will be a prospective cohort of HIV-1 infected women followed for up to 10 years. The study outcomes will be mortality, the development of AIDS-defining conditions and cervical disease. Predictor variables will be cigarette smoking, genetic polymorphisms, albumin, prealbumin and CRP. Covariates will include CD4 cell count, HIV RNA, age at enrollment and antiretroviral therapy.